Neuronal apoptosis plays a critical event in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). This study investigated the roles of Tauroursodeoxycholic acid (TUDCA) in attenuate neuronal apoptosis and underlying mechanisms after SAH. Sprague–Dawley rats were subjected to model of SAH and TUDCA was administered via the internal carotid injection. Small interfering RNA (siRNA) for TGR5 were administered through intracerebroventricular injection 48 h before SAH. Neurological scores, brain water content, Western blot, TUNEL staining and immunofluorescence staining were evaluated. TUDCA alleviated brain water content and improved neurological scores at 24 h and 72 h after SAH. TUDCA administration prevented the reduction of SIRT3 and BCL-2 expressions, as well as the increase of BAX and cleaved caspase-3.Endogenous TGR5 expression were upregulated after SAH and treatment with TGR5 siRNA exacerbated neurological outcomes after SAH and the protective effects of TUDCA at 24 h after SAH were also abolished by TGR5 siRNA. Our findings demonstrate that TUDCA could attenuated neuronal apoptosis and improve neurological functions through TGR5/ SIRT3 signaling pathway after SAH. TUDCA may be an attractive candidate for anti-apoptosis treatment in SAH.

中文翻译：

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蛛网膜下腔出血后牛磺去氧胆酸通过TGR5 / SIRT3途径减轻神经元凋亡

神经元凋亡在蛛网膜下腔出血（SAH）后早期脑损伤的发病机理中起关键作用。这项研究调查了牛磺去氧胆酸（TUDCA）在减轻SAH后神经元凋亡及其潜在机制中的作用。对Sprague–Dawley大鼠进行SAH模型治疗，并通过颈内动脉注射给予TUDCA。在SAH前48小时通过脑室内注射TGR5的小干扰RNA（siRNA）。评价神经学评分，脑含水量，蛋白质印迹，TUNEL染色和免疫荧光染色。TUDCA减轻了SAH后24 h和72 h的脑含水量并改善了神经学评分。施用TUDCA可以防止SIRT3和BCL-2表达的减少，以及BAX和裂解的caspase-3的增加。SAH后内源性TGR5表达上调，TGR5 siRNA的治疗加重了SAH的神经系统预后，TGR5 siRNA也取消了SAH后24 h TUDCA的保护作用。我们的发现表明，TUDCA可以通过SAH后的TGR5 / SIRT3信号传导途径减轻神经元凋亡并改善神经功能。TUDCA可能是SAH中抗凋亡治疗的有吸引力的候选药物。